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Updated: Jun 14, 2026
Isolation and Enrichment of Human Lung Epithelial Progenitor Cells for Organoid Culture
Published on: July 21, 2020
Identification of SARS-CoV-2 inhibitors using lung and colonic organoids
Yuling Han1, Xiaohua Duan1,2, Liuliu Yang1
1Department of Surgery, Weill Cornell Medicine, New York, NY, USA.
Abstract:
There is an urgent need to create novel models using human disease-relevant cells to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biology and to facilitate drug screening. Here, as SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs). The hPSC-LOs (particularly alveolar type-II-like cells) are permissive to SARS-CoV-2 infection, and showed robust induction of chemokines following SARS-CoV-2 infection, similar to what is seen in patients with COVID-19. Nearly 25% of these patients also have gastrointestinal manifestations, which are associated with worse COVID-19 outcomes1. We therefore also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-LOs, we performed a high-throughput screen of drugs approved by the FDA (US Food and Drug Administration) and identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid and quinacrine dihydrochloride. Treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs. Together, these data demonstrate that hPSC-LOs and hPSC-COs infected by SARS-CoV-2 can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.
Insights
Researchers developed human lung and colon organoids to model SARS-CoV-2 infection. These organoids identified FDA-approved drugs, like imatinib, that inhibit viral entry, offering new COVID-19 therapeutic strategies.
Area of Science:
- Stem cell biology
- Virology
- Drug discovery
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, necessitating better models for studying its biology and developing treatments.
- Existing models often lack human disease relevance, limiting their utility for drug screening and understanding pathogenesis.
Purpose of the Study:
- To develop human pluripotent stem cell-derived lung (hPSC-LOs) and colonic organoids (hPSC-COs) as models for SARS-CoV-2 infection.
- To investigate the permissiveness of these organoids to SARS-CoV-2 and their inflammatory responses.
- To conduct a high-throughput drug screen using hPSC-LOs to identify potential COVID-19 therapeutics.
Main Methods:
- Generation of hPSC-LOs and hPSC-COs from human pluripotent stem cells.
- Infection of organoids with SARS-CoV-2 to assess permissiveness and chemokine induction.
- High-throughput screening of FDA-approved drugs using hPSC-LOs.
- Validation of drug efficacy in inhibiting SARS-CoV-2 infection in both hPSC-LOs and hPSC-COs.
Main Results:
- hPSC-LOs, particularly alveolar type-II-like cells, were susceptible to SARS-CoV-2 infection and induced chemokines, mimicking COVID-19 patient responses.
- hPSC-COs, including enterocytes, expressed ACE2 and were permissive to SARS-CoV-2 infection.
- Drug screening identified imatinib, mycophenolic acid, and quinacrine dihydrochloride as SARS-CoV-2 entry inhibitors.
- These identified drugs significantly inhibited viral infection in both lung and colon organoids at physiological concentrations.
Conclusions:
- hPSC-LOs and hPSC-COs provide robust, human disease-relevant models for studying SARS-CoV-2 infection.
- These organoid models are valuable for high-throughput drug screening and identifying candidate therapeutics for COVID-19.
- The identified entry inhibitors represent promising avenues for further investigation as COVID-19 treatments.
